Abstract
A novel Plasmodium falciparum gene, MB2, was identified by screening a sporozoite cDNA library with the serum of a human volunteer protected experimentally by the bites of P. falciparum-infected and irradiated mosquitoes. The single-exon, single-copy MB2 gene is predicted to encode a protein with an M(r) of 187,000. The MB2 protein has an amino-terminal basic domain, a central acidic domain, and a carboxyl-terminal domain with similarity to the GTP-binding domain of the prokaryotic translation initiation factor 2. MB2 is expressed in sporozoites, the liver, and blood-stage parasites and gametocytes. The MB2 protein is distributed as a approximately 120-kDa moiety on the surface of sporozoites and is imported into the nucleus of blood-stage parasites as a approximately 66-kDa species. Proteolytic processing is favored as the mechanism regulating the distinct subcellular localization of the MB2 protein. This differential localization provides multiple opportunities to exploit the MB2 gene product as a vaccine or therapeutic target.
Highlights
A novel Plasmodium falciparum gene, MB2, was identified by screening a sporozoite cDNA library with the serum of a human volunteer protected experimentally by the bites of P. falciparum-infected and irradiated mosquitoes
We report the characterization of MB2, a novel gene encoding a P. falciparum sporozoite surface antigen identified by screening a CS-depleted sporozoite expression cDNA library with serum from a human volunteer protected by the bites of P. falciparum-infected and irradiated mosquitoes
The Northern analyses with mRNA obtained from the blood-stage parasites indicated that MB2 is expressed as a single large transcript
Summary
Vol 276, No 28, Issue of July 13, pp. 26724 –26731, 2001 Printed in U.S.A. Stage-dependent Localization of a Novel Gene Product of the Malaria Parasite, Plasmodium falciparum*. A novel Plasmodium falciparum gene, MB2, was identified by screening a sporozoite cDNA library with the serum of a human volunteer protected experimentally by the bites of P. falciparum-infected and irradiated mosquitoes. Proteolytic processing is favored as the mechanism regulating the distinct subcellular localization of the MB2 protein This differential localization provides multiple opportunities to exploit the MB2 gene product as a vaccine or therapeutic target. Experimental support for the development of a vaccine for human malaria was provided first by the use of radiationattenuated sporozoites as immunogens [3] The success of this experimental vaccination provided the impetus for the search for mechanisms of protective immune responses and the target antigens involved. We report the characterization of MB2, a novel gene encoding a P. falciparum sporozoite surface antigen identified by screening a CS-depleted sporozoite expression cDNA library with serum from a human volunteer protected by the bites of P. falciparum-infected and irradiated mosquitoes. This differential localization provides multiple opportunities to exploit the MB2 gene product as a vaccine and drug target
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